Lipase catalysis was successfully employed to synthesize high molecular weight poly(butylene succinate) (PBS). Attempts to copolymerize succinic acid with 1,4-butanediol were unsuccessful due to phase separation of the reactants. To circumvent this problem, monophasic reaction mixtures were prepared from diethyl succinate and 1,4-butanediol. The reactions were studied in bulk as well as in solution. Of the organic solvents evaluated, diphenyl ether was preferred, giving higher molecular weight products. After 24 h in diphenyl ether, polymerizations at 60, 70, 80, and 90 degrees C yielded PBS with M-n of 2000, 4000, 8000, and 7000, respectively. Further increase in reaction time to 72 h resulted in little or no further increase in M-n. However, increasing the reaction time produced PBS with extraordinarily low M-w/M-n due to the diffusion and reaction between low-molecular weight oligomers and chains that occurs at a greater frequency than interchain transesterification. Time-course studies and visual observation of polymerizations at 80 degrees C revealed PBS precipitates at 5 to 10 h, limiting the growth of chains. To maintain a monophasic reaction mixture, the polymerization temperature was increased from 80 to 95 degrees C after 21 h. The result was an increase in the PBS molecular weight to M-w = 38 000 (M-w/M-n = 1.39). This work paves the way for the synthesis of PBS macromers and polymers that contain variable quantities of monomers with chemically sensitive moieties (e.g., silicone, epoxy, vinyl). Furthermore, this study established the feasibility of using lipase catalysis to prepare polyesters from alpha,omega-linear aliphatic diethyl ester/diol monomers with less than six carbons.